I. What every physician needs to know.

Cytomegalovirus (CMV) colitis is the second most common presentation of CMV in the immunocompromised patient. It is classically reported in patients with human immunodeficiency virus (HIV), but it has also been seen in patients with impaired immune systems from corticosteroid therapy or immune-modulating drugs for autoimmune disease and in the post-transplant setting (both solid organ and bone marrow). In truly immunocompetent patients, CMV colitis is rare but has been reported in patients with steroid use or RBC transfusion in the prior month.

CMV colitis should be suspected in immunocompromised patients presenting with the symptoms below; colonic involvement may also be heralded by tenesmus, frequent, watery stools and/or hemtaochezia as its primary symptoms.

A. History Part I: Pattern Recognition:

Abdominal pain

Diarrhea (sometimes low volume, frequent)

Low grade fever

Weight loss

Anorexia

Tenesmus

Hematochezia

B. History Part 2: Prevalence:

CMV colitis was first described in the HIV population in the early 1980's; prior to highly active antiretroviral (HAART) therapy it had high morbidity and mortality. It is most commonly seen now in patients not on HAART therapy, with a cluster of differentiation 4 (CD4) count less than 200.

CMV colitis is increasingly being recognized as a complicating factor in exacerbations of IBD, severe cases, and steroid-resistant cases of IBD. Whether CMV reactivation exacerbates the disease in patients with established IBD or is an epiphenomenon of IBD activity is still being investigated.

C. History Part 3: Competing diagnoses that can mimic cytomegalovirus colitis.

A complete work-up for other infectious etiologies should be undertaken, as CMV colitis is one of many infectious agents that can cause diarrhea in an immunocompromised host. For further information on the differential diagnosis of diarrhea in a HIV+ patient, please see the relevant chapter.

D. Physical Examination Findings.

Physical exam is often not specific to the diagnosis of CMV colitis; fever in these patients can be indicative of an infectious etiology. Care should be taken to look for peritoneal signs, as perforation of the involved colon can occur in severe cases of CMV colitis.

E. What diagnostic tests should be performed?

Colonoscopy with biopsy is the gold standard. The affected bowel may appear grossly with small erosions, or be severely involved with deep, necrotizing lesions. Biopsy will reveal intranuclear or intracytoplasmic inclusion bodies in the endotheial cells; inflammatory changes will be present at the edges of the ulcerated areas. Occasionally CMV colitis will manifest as large ulcers in the rectal region; isolated right-sided CMV colitis has also been reported.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

CMV IgM and IgG blood testing are highly specific and sensitive for acute infection and prior exposure respectively. CMV viremia can be detected by polymerase chain reaction (PCR) test. Blood testing for CMV with the before mentioned tests may be misleading, as serologic evidence of CMV may be present without active pathologic disease. Likewise, CMV culture in stool also does not reliably correlate with target organ involvement and may occur as asymptomatic viral shedding.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Computed tomography (CT) scan of the abdomen may show inflammatory changes within the colon, but is non-diagnostic. Colonoscopy with biopsy is the gold standard.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

See CMV viremia, serology, and stool culture as above.

III. Default Management.

Management as an inpatient is likely necessary for the induction phase of antiviral therapy; supportive inpatient care may be necessary depending upon the severity of presentation and symptoms. Care can then be transitioned to the outpatient setting for completion of the course.

A. Immediate management.

The drug of choice is ganciclovir (5 mg/kg twice daily) for immunocompromised patients; this should be continued for 3 to 6 weeks, although conversion from intravenous to oral for completion of the course once symptoms have improved is acceptable. Alternatively, foscarnet (90 mg/kg twice daily) may be used for 3 to 6 weeks.

Oral maintenance therapy with valganciclovir after completion of the induction phase is generally reserved for immunocompromised individuals who have suffered a relapse of the CMV gastrointestinal (GI) disease. Valganciclovir should not be used for induction therapy in immunocompromised hosts.

D. Long-term management.

E. Common Pitfalls and Side-Effects of Management

A. Renal Insufficiency.

Caution with foscarnet; ganciclovir may be preferred in patients with renal insufficiency.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard management.

E. Diabetes or other Endocrine issues

No change in standard management.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

HAART therapy should be started once symptoms are improving in patients with HIV not previously on therapy.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

Concurrent CMV esophagitis: no change in therapy.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

A. Sign-out considerations While Hospitalized.

No specific follow-up/sign-out issues.

B. Anticipated Length of Stay.

Varied based upon clinical presentation; when patients are able to tolerate an oral regimen and symptoms are under control, they may be discharged for completion of antiviral therapy.

C. When is the Patient Ready for Discharge.

As above.

D. Arranging for Clinic Follow-up

A repeat endoscopy to document mucosal healing may be warranted, especially in patients who complete 2 to 3 weeks of therapy and still have symptoms. This can be particularly important in the immunocompromised host.

1. When should clinic follow up be arranged and with whom.

Infectious diseases follow-up for HAART therapy if the patient is newly diagnosed with HIV; GI follow-up in 2-4 weeks for follow-up colonoscopy to document healing, if desired by the consultant.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

NA

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Colonoscopy if desired by GI.

E. Placement Considerations.

NA

F. Prognosis and Patient Counseling.

CMV colitis in HIV infected individuals typically responds to treatment and does not recur if immune reconstitution is achieved with highly active antiretroviral therapy (HAART). In IBD patients, response rate to antiviral therapy is 72% (range 50% to 83%).

A. Core Indicator Standards and Documentation.

NA

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Valganciclovir may be used for suppression if patients have suffered from a relapse of CMV colitis.

**The original author for this chapter was Dr. Nicole A. Swallow. The chapter was revised by Dr. James D. Alstott.